Azelastine is a phthalazinone derivative having the following structural formula: ##STR1##
The chemical designation is: 4-(4-chlorobenzyl)-2-(perhydro-1-methylazepine-4-yl)-1-(2H) phthalazinone. Azelastine is used in particular in asthma prophylaxis. Azelastine also has anti-allergic and antihistaminic properties, see German Patent No. 21 64 058.
One of the main disadvantages of using azelastine is that it makes the patients tired. Many patients also report drowsiness, giddiness and the like. These side effects develop especially during the first days of azelastine therapy, and preclude the patients from operating motor vehicles or machinery. There is a general loss of alertness.
Therefore, it would be highly desirable, and would be regarded as an important medical advance, if azelastine could be administered to patients which did not cause these side effects.
In the past, these side effects have been conventionally alleviated by supplying a combination medication which contained both the active substance which made the patient tired and caffeine. The caffeine was intended to antagonize the sedative property of the active substance. However, this procedure cannot be used in the case of azelastine since the elimination half lives t.sub.1/2 (t.sub.1/2 is the time within which the serum level of the active substance in the blood diminishes without further active substance intake from a specific starting value to half this value) of azelastine and caffeine differ very greatly from one another: the t.sub.1/2 of azelastine is 20 hours whereas the t.sub.1/2 of caffeine is only 3.5 hours. Therefore, it is to be expected that, if azelastine and caffeine are administered together, the effect of the caffeine will decrease after a certain time, and the sedative effect of the azelastine will once again become apparent.
The conventional approach is then to delay the release of the active substance--caffeine--in the dosage form so much that a prolonged time of efficacy results. This procedure is, however, linked with the difficulty of adjusting the blood level rates of the two active substances in vivo so that they are as similar as possible. This is not possible, using techniques presently available, because of the large differences in the elimination rates.
A further problem with azelastine is its extremely unpleasant taste. The taste is so unpleasant that, for example, liquid azelastine formulations (for example juice) are not taken, or even refused, by patients, in particular by children.